• Radiation Oncology Journal
• /
• v.31 no.2
• /
• pp.57-65
• /
• 2013

Beta-lapachone (${\beta}$-Lap; 3,4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5,6-dione) is a novel anti-cancer drug under phase I/II clinical trials. ${\beta}$-Lap has been demonstrated to cause apoptotic and necrotic death in a variety of human cancer cells in vitro and in vivo. The mechanisms underlying the ${\beta}$-Lap toxicity against cancer cells has been controversial. The most recent view is that ${\beta}$-Lap, which is a quinone compound, undergoes two-electron reduction to hydroquinone form utilizing NAD(P)H or NADH as electron source. This two-electron reduction of ${\beta}$-Lap is mediated by NAD(P)H:quinone oxidoreductase (NQO1), which is known to mediate the reduction of many quinone compounds. The hydroquinone forms of ${\beta}$-Lap then spontaneously oxidizes back to the original oxidized ${\beta}$-Lap, creating futile cycling between the oxidized and reduced forms of ${\beta}$-Lap. It is proposed that the futile recycling between oxidized and reduced forms of ${\beta}$-Lap leads to two distinct cell death pathways. First one is that the two-electron reduced ${\beta}$-Lap is converted first to one-electron reduced ${\beta}$-Lap, i.e., semiquinone ${\beta}$-Lap $(SQ)^{{\cdot}-}$ causing production of reactive oxygen species (ROS), which then causes apoptotic cell death. The second mechanism is that severe depletion of NAD(P)H and NADH as a result of futile cycling between the quinone and hydroquinone forms of ${\beta}$-Lap causes severe disturbance in cellular metabolism leading to apoptosis and necrosis. The relative importance of the aforementioned two mechanisms, i.e., generation of ROS or depletion of NAD(P)H/NADH, may vary depending on cell type and environment. Importantly, the NQO1 level in cancer cells has been found to be higher than that in normal cells indicating that ${\beta}$-Lap may be preferentially toxic to cancer cells relative to non-cancer cells. The cellular level of NQO1 has been found to be significantly increased by divergent physical and chemical stresses including ionizing radiation. Recent reports clearly demonstrated that ${\beta}$-Lap and ionizing radiation kill cancer cells in a synergistic manner. Indications are that irradiation of cancer cells causes long-lasting elevation of NQO1, thereby sensitizing the cells to ${\beta}$-Lap. In addition, ${\beta}$-Lap has been shown to inhibit the repair of sublethal radiation damage. Treating experimental tumors growing in the legs of mice with irradiation and intraperitoneal injection of ${\beta}$-Lap suppressed the growth of the tumors in a manner more than additive. Collectively, ${\beta}$-Lap is a potentially useful anti-cancer drug, particularly in combination with radiotherapy.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.42 no.2
• /
• pp.129-133
• /
• 1997

A total 943 accession of soybeans (G. max) and 50 wild soybeans (G. soja) were examined for leucine aminopeptidase (LAP) isozyme variation by 5％ polyacrylamide gel electrophoresis(PAGE) and isoelectric focusing(IEF) of pH 4~6.5. The Lap1*b by PAGE was the most common phenotype in both G. max and G. soja. The frequency of Lap1*b allele was observed to be higher in G. max(1.00) than in G. soja(0.96) of Korea. This result shows that G. max is fixed for Lapl*b allele at the Lap1 locus. LAP isozyme band type I and II were found using IEF of pH 4~6.5 in G. max and G. soja of Korea. Type I was observed from 92.8％ in G. max and 92.0％ in G. soja, and type II was discovered in 7.2％ G. max and 8.0％ G. soja. This result suggested the possibility to be found more various band types.

• Proceedings of the KSR Conference
• /
• 2005.05a
• /
• pp.326-331
• /
• 2005

In this study, bearing response in single lap riveted joint is investigated by menas of single lap shear specimens with different types of adherend and fastener. Single lap shear specimen consists of adherend of SUS403 and carbon fabric/epoxy composite. Rivet of Avdel 2691 with 9.6mm diameter is used. Two types of fastener in single lap riveted joint are considered. One is a single lap shear specimen with single fastener, and the other is a single lap shear specimen with double fasteners. Especially, in case of single lap shear specimen with single fastener, the width of the specimen is varied as 2D, 3D, 4D, 6D at a fixed edge distance of 3D. Also the edge distance of the specimen is varied as 1.0D, 1.5D, 2.0D, 2.5D, 3.0D at a fixed width of 4D. In case of single lap shear specimen with double fasteners, two types of specimen are considered. One is a specimen with the width of 6D and edge distance of 3D. The other is a specimen with the width of 4D and edge distance of 2D. Here D designates the hole diameter for riveted joint.

• Transactions of the Korean Society of Mechanical Engineers
• /
• v.18 no.1
• /
• pp.85-92
• /
• 1994

With the wide application of fiber-reinforced composite meterial in aircraft space structures and robot arms, the design and manufacture of composite joints have become a very important research area because they are often the weakest areas in composite structure. In this paper, the torque transmission capacities of the adhesive tubular single lap joint and double lap joint were studied. The stress and torque transmission capacity of the adhesive joints were analyzed by the finite element method and compared to the experimental results. The torque capacity of the double lap joint was increased 2.7 times over that of the single lap joint. Also, the fatigue limit of the double lap joint was increased 16 times over that of the single lap joint.

• Journal of Korean Society of Forest Science
• /
• v.43 no.1
• /
• pp.39-50
• /
• 1979

Twelve Pinus taeda were used as mother trees and one P. rigida plus tree was used as pollen tree for 12 cross combinations. Nine P. densiflora plus trees(4 mother and 7 pollen trees) were used as parents for 11 cross combinations. Those parents and 10 progenies were analyzed for LAP of ${\times}$P. taeda rigida hybrid and P. densiflora and for peroxidase of ${\times}$P. taeda rigida. The analysis, based on the banding patterns, indicate three alleles for LAP-A locus(A1, A2, A3) and two alleles for LAP-B locus (B1, B2) in ${\times}$P. taeda rigida hybrids. Chi-square test on the segregation for progenies did not show significant differences. The results indicated good agreement with monohybrid Mendelian inheritance. Independence test for occurrence frequency of 2 alleles(LAP-A3, LAP-B2) illustrated that there is neither linkage nor repulsion relationship between LAP-A3 and LAP-B2 alleles. Three band at LAP-A locus were always exhibited from all parents and their progenies of P. densiflora. However, the occurrence of two bands at LAP-B locus was variable, one bands assumed as homozygous alleles(B2/B2) and two bands as heterozygous alleles(B1/B2). The segregation ratio for progenies of P. densiflora suggested that LAP-B locus may be controlled by two alleles(B1 and B2). Three Peroxidase loci(Px-A, Px-B, Px-C) assumed to be controlled by allozyme in ${\times}$P. taeda rigida hybrid. The Px-B and Px-C loci could not find out the variations from banding patterns of parents and their progenies, while the Px-A locus showed the variations of occurrence frequency by two bands. The segregation ratio for A1/A2 at LAP-A locus suggest that the peroxidase allozymes of ${\times}$P. taeda rigida hybrid appeare to be monomeric products; that is, Px-A locus may be controlled by two alleles (A1 and A2).

• Journal of Welding and Joining
• /
• v.12 no.1
• /
• pp.102-115
• /
• 1994

This paper is to evaluate the fatigue strength of lap joints of materials applied to LNG carrier cargo containment of GAZ-TRANSPORT(GT) type, which was welded by manual and automatic TIG welding process. The thicknesses of lapped members were 1.5mm/1.5mm or 1.5mm/0.7mm in Invar to Invar joint, and 1.5mm/8.0mm in Invar to stainless steel joint, respectively. These lap joints were mainly applied to the membrance fabrication of GT-LNG carrier. Fatigue tests of Invar/Inar lap joints were conducted under the stress ratio R=0 at room temperature. The effect of mean stress and cumulative fatigue damage on the allowable stress of Invar lap joint was evaluated on the basis of test results. Fatigue test was also conducted on Inver/Stainless steel lap joints welded by automatic TIG process without filler metals. The fatigue test of the joint was carried out under the same conditions as those of Invar/invar lap joints. The fatigue strength of the joint welded without filler metal was comparable to those welded with filler metal quoted from reference. The fatigue strength of Invar/stainless steel lap joint was only dependent on the lap throat thickness, and not on the welding process. Based on test results, the applicability of TIG welding process without filler metal in Invar/stainless steel lap joint was reviewed by controlling welding variables to assure the valid throat thickness of lap joints.

• International Journal of Korean Welding Society
• /
• v.4 no.1
• /
• pp.53-60
• /
• 2004

Adhesive-bonded joints are widely used in the industry. Recently, applications of adhesive bonding joints have been increased extensively in automobile and aircraft industry. The strength of adhesive joints is influenced by the surface roughness, adhesive shape, stress distribution, and etc. However, the magnitude of the influence has not yet been clarified because of the complexity of the phenomena. In this study, as the fundamental research of adhesive bonding joints, the effects of adhesive shape and loading speed on bonding strength properties and durability of aluminum to polycarbonate single-lap joints were studied. To evaluate the effect of adhesive shape, several modified shapes were used, and loading speeds were varied from 0.05 to 5mm/min. As a result, the load distribution showed a brittle fracture tendency. The trigonal edged single lap and bevelled lap joints showed the higher strength than the plain single lap, trigonal single lap, joggle lap and double lap joints in same adhesive area. The fractures of trigonal single lap and trigonal edged single lap joints that had the higher strength level were shown as the mixture type of the cohesive and interfacial-failure, mostly joggle lap joints that had the lower strength level were shown as the adhesive-failure.

• Biomolecules & Therapeutics
• /
• v.32 no.5
• /
• pp.531-539
• /
• 2024

Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A₁ receptor (A₁R) antagonist. Western blot analysis showed that β-Lap increased extracellular signal-regulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A₁R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A₁R.

• Proceedings of the Korean Biophysical Society Conference
• /
• 2003.06a
• /
• pp.80-80
• /
• 2003

${\beta}$-lapachone(${\beta}$-Lap), a natural o-naphthoquinone, presents in the bark of the Lapacho tree. ${\beta}$-Lap is cytotoxic against a variety of human cancer cells and it potentiates the anti-tumor effect of Taxol. In addition, ${\beta}$-Lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage.In the present study, we investigated the cytotoxicity of ${\beta}$-Lap against RKO human colorectal cancer cells as well as the combined effect of ${\beta}$-LaP and ionizing radiation. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h killed almost 90％ of the clonogenic cells. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h or longer also caused massive apoptosis. Unlike other cytotoxic agents, ${\beta}$-Lap did not increase the expression of p53 and p21 and it suppressed the NFkB expression. The expression of Caspase 9 and 3 was minimally altered by ${\beta}$-Lap. Radiation and ${\beta}$-Lap acted synergistically in inducing clonogenic cell death and apoptosis in RKO cells when ${\beta}$-Lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 ${\mu}$M of ${\beta}$-Lap starting 5 h after irradiation was as effective as that starting immediately after irradiation. The mechanisms of ${\beta}$-Lap-induced cell killing is controversial but a recent hypothesis is that ${\beta}$-Lap is activated by NAD(P)H: quinone-onidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca$\^$2+/ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated for longer than 10 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 5h after 2-4 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the ${\beta}$-Lap treatment applied S h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the ${\beta}$-Lap treahment applied 5 h after irradiation could not inhibit the repair of radiation-induced damage. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm3 tumor. The mice were i.p. injected with ${\beta}$-lapachone or saline 2 h after irradiation of tumors with 10 Gy of X-rays. The radiation induced growth delay was increased by 2.4 $\mu\textrm{g}$/g of ${\beta}$-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and ${\beta}$-Lap in killing cancer cells is not due to radiosensitization by ${\beta}$-Lap but to an enhancement of ${\beta}$-Lap cytotoxicity by radiation through an upregulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using ${\beta}$-Lap in combination with radiotherapy.

• Structural Engineering and Mechanics
• /
• v.37 no.1
• /
• pp.95-110
• /
• 2011

This paper presents a tri-uniform bond stress model for predicting the lap splice strength of reinforcing bar at the critical bond splitting failure. The proposed bond distribution model consists of three zones, namely, splitting zone, post-splitting zone and yielding zone. In each zone, the bond stress is assumed to be constant. The models for bond strength in each zone are adopted from previous studies. Combining the equilibrium, strain-slip relation and the bond strength model in each zone, the steel stress-slip model can be derived, which can be used in the nonlinear frame analysis of the column. The proposed model is applied to derive explicit equations for predicting the strength of the lap splice strengthened by fiber reinforced polymer (FRP) in both elastic and post-yield ranges. For design purpose, a procedure to calculate the required FRP thickness and the number of FRP sheets is also presented. A parametric investigation was conducted to study the relation between lap splice strength and lap splice length, number and thickness of FRP sheets and the ratio of concrete cover to bar diameter. The study shows that the lap splice strength can be enhanced by increasing one of these parameters: lap splice length, number or thickness of FRP sheets and concrete cover to bar diameter ratio. Verification of the model has been conducted using experimental data available in literature.